N-Vinyl-2-pyrrolidone (NVP) is a monomer used for making crosslinked or uncrosslinked polyvinylpyrrolidones, vinyl pyrrolidone-vinyl ester copolymers, and other valuable polymers. The polymers are used in beverage clarification, hair care, pharmaceutical tablet binding, and other industrial applications.
NVP is commonly purified by fractional distillation to remove unreacted starting materials and side-products. For a recent example, see U.S. Pat. No. 6,436,243. It can also be purified by treatment with an acidic ion-exchange resin (see U.S. Pat. No. 5,039,817). Fractional distillation provides “industrial grade” NVP that is 98–99.5% pure, but this purity level can be inadequate for beverage clarification, cosmetics, and pharmaceutical uses. In particular, industrial grade NVP often contains traces of close-boiling impurities such as 2-pyrrolidone (2-Py), N-ethylpyrrolidone (NEP), and gamma-butyrolactone (GBL).
Multi-stage, melt crystallization is used to upgrade industrial grade NVP to “pharmaceutical grade” NVP, which is more than 99.9% pure, and often more than 99.99% pure. The process is costly, requires expensive equipment, and is time-consuming. In a melt crystallization process, NVP is cooled below 14° C. (its nominal freezing point) to promote crystallization. As crystals form, they are separated from the mother liquor. The process is repeated to achieve a desired purity level. Unfortunately, because the NVP is usually quite pure already, the temperature must be controlled with great care to prevent the entire mass from rapidly solidifying or to prevent already-crystallized NVP from melting back into the mother liquor. Separating and handling crystals that are at a temperature only slightly below their melting point is difficult, as the crystals tend to melt quickly with even a slight temperature increase or disturbance.
U.S. Pat. No. 5,329,021 describes a melt crystallization process in which NVP is cooled 1° C. to 5° C. below its freezing point to induce crystal formation, the crystals are separated from the remaining mother liquor and are liquified, and the purified liquid is subjected to one or more additional crystallization stages. This process suffers from the need for careful temperature control, rapid freezing of supercooled liquid to a solid mass, and rapid melting of isolated crystals. Thus, there is a premium on the ability to control temperature accurately and precisely. The tight temperature window makes it difficult to separate the crystals from the mother liquor, thus reducing the efficacy of the crystallization step.
In another approach, crystallizer surfaces are covered with a seed layer of crystallized NVP to induce crystallization of the impure NVP liquid (see U.S. Pat. Nos. 5,710,284 and 5,755,975). This method reduces the reliance on supercooling but otherwise suffers from most of the drawbacks noted above.
U.S. Pat. No. 6,703,511 teaches to improve the crystallization process by adding a side-purification routine. Mother liquor from the first crystallization stage is distilled or is subjected to an extractive workup to remove impurities. The purified mother liquor is then returned to the crystallizer. An ideal crystallization method for NVP would sidestep supplemental purification schemes.
The industry would benefit from better ways to purify NVP. In particular, an improved way of crystallizing industrial grade NVP to produce pharmaceutical grade NVP is needed. Preferably, the method would overcome the need for expensive equipment, precise temperature control, multiple crystallizations, or seeding techniques. An ideal method would provide NVP crystals that can be easily isolated from the mother liquor and can be handled or transferred without rapid remelting.
Recently, we found that adding water to NVP depresses both the melting and freezing points of the NVP/water mixture, but it does so differentially. This interesting observation prompted us to devise conditions under which NVP can be effectively and efficiently purified by crystallization.